Embodiments of the present invention relate to the field of drug delivery and encompass drug-delivery devices driven by an electrically-controlled displacement-generating battery cell. More particularly, embodiments of the present invention relate to an electrically-controlled non-gas evolution dependent volume-changing or shape-changing electrochemical cell, which drives a drug-delivery mechanism, wherein the delivery rate can be very precisely controlled.
There are numerous kinds of electrochemical cells, the common element being that applying an electrical charge to or removing an electrical charge from such a cell causes an electrochemical change, and in some cases a derived chemical change in the electrodes, and in some cases also the electrolyte of such cell. Many types of electrochemical cells comprise electrodes and electrolyte, in which the chemical reaction between said chemicals in the cell is driven by discharging or charging said electrodes. Such a cell can be either a passive cell or a battery cell. In a passive cell, electricity needs to be introduced into the cell in order to “drive” the chemical reaction. In a battery cell or fuel cell, the cell itself generates electricity as the reaction runs, providing that a discharge circuit is connected to the cell positive and negative poles. In the case of a passive cell (or a battery on charge), the rate of reaction is determined by the electrical power applied; whereas in a battery cell which is discharging, the control over the energy consumption determines the rate of discharge of the battery. The definition of battery cells herein includes not only conventional types of batteries (using either “wet” or “dry” chemistry) but also (a) lithium “shuttle” type batteries in which the process is that ions in the electrolyte shuttle back and forth between the electrodes as opposed to participating in a conventional chemical reaction; and (b) sealed fuel cells in which a fixed starting amount of fuel is used up as the cell discharges. Embodiments of the present invention apply to all the above types of cells, providing only that the electrochemical and/or derived chemical process involved is such that it causes a volume change or shape change within the cell as the process proceeds.
In the field of battery cells, the volume change generated as the battery charges or discharges is a known yet undesirable side effect, said effect being mentioned in the various references. For example, US Patent Publication No. 2004/0115530 describes a method of preventing the detrimental effects of the volume change of the active material in a lead-acid battery cell. However, in embodiments of the present invention, such “undesirable” volume changes are exploited in order to provide a useful feature: precise, controlled drug-delivery such as that required for slow-infusion or medical devices. A benefit is that this enables increased control over the delivery of liquid drugs via a programmable electronic system.
Embodiments of the present invention relate to an interesting demonstration of how physical changes that occur in batteries during discharge can be exploited for performing useful mechanical work. Conventional batteries are used to convert chemical energy into electrical energy. We report here on batteries where this conversion is instead optimized for supplying mechanical energy derived from large increases that occur in the volume of an anode, cathode, or both, as the cell is discharged. Such physical expansion of the anode, cathode, or both electrodes is expressed as increasing cell height in such cells sealed in an expandable housing. This axial expansion can add significantly to original height making them attractive as simple self-powered mechanical actuators for various devices. As such cells can be made with a range of initial heights, multi-millimeter expansions are achieved with generation of forces of more than 1 Kg/cm2 per electrode cross-sectional area. Control of both the rate at which the height increases and the total expansion is accomplished by normal regulation of discharge.
In one example application, such battery cells compress a semi-flexible drug reservoir in a drug delivery pump pushing fluid into an attached tubing that delivers the medication for sub-cutaneous injection via a soft cannula. The pump can operate for several days. Dosing levels can be controlled from fast deliveries of several hours down to several tens of microliters per hour with high accuracy. The technology is designed to deliver drug volumes of 1 to about 10 cc which are in the range between that delivered by syringes and that of infusion drip bags.
Numerous types of inexpensive drug-delivery mechanisms are known, typically employing a gas-driven infusion principle. U.S. Pat. Nos. 5,318,557 and 5,527,288 describe an inexpensive, gas-driven infusion device which can be manufactured sufficiently inexpensively in order to constitute a disposable product. The embodiments described therein employ an electrolytic cell for gas production as per U.S. Pat. No. 5,062,834. A similar gas-driven device is described in U.S. Pat. No. 5,354,264. This device utilizes gas pressure from free oxygen and hydrogen derived from the electrolysis of water at the electrodes in negatively charged polymeric hydrogels. Said device ensures that the gas generated remains within the walls of the gas chamber by making said walls “rigid and impermeable to gases”. In all these devices, the gas pressure forces the infusion of the drugs through appropriate means into the body, with the pressure being dependent on the rate of electrolysis, which is in turn controlled by an electric current. A further class of devices uses the same gas-driven principle, but generates this gas by chemical rather than electrical means. For example, U.S. Pat. No. 5,814,020, hereby incorporated by reference, describes a gas-powered infusion device where the gas is generated either by an electrolytic cell or by the reaction between citric acid and sodium bicarbonate; said reaction generating carbon dioxide and water.
The central problem with these gas-driven devices is that they all employ a gas-filled chamber in order to drive the drug infusion. As gases are very susceptible to changes in ambient temperature and air pressure, the danger of employing this principle is that a significant and undesirable change in the flow-rate will occur as such temperature or pressure changes occur. For example, a loss of pressure in an airplane could result in a sudden bolus being delivered at an inappropriate time. Similarly, a drop in temperature could result in the drug infusion stopping. For these reasons, despite massive development efforts, these products have faced considerable commercial obstacles to implementation. The literature confirms the problematic nature of this issue. In a partial attempt to address this issue, U.S. Pat. No. 6,186,982 describes a flow-regulation chamber appropriate to the above-described devices which attempts to compensate for such temperature and/or pressure changes. Nonetheless, this issue of heat and pressure sensitivity is an inherent disadvantage inhibiting the commercialization of these products. Additionally, even when the surrounding conditions are constant, these technologies suffer from the disadvantage of providing a time-lagged response to the control system. For example, if the system's control requires a complete halt of the drug delivery, the residual gas pressure will keep pushing the drug out.
Further known technology in this field includes (a) MEMS-based pumps in which a miniature pump is implemented on a silicon chip using integrated-circuit fabrication techniques, such as the Chronojet™ from Debiotech S. A. (Lausanne, Switzerland); (b) those in which a piezo-electric pumping mechanism is used such as U.S. Pat. No. 6,589,229; and (c) those which use SME wire technology such as the OmniPod™ product from Insulet, Inc. (Bedford, Mass., USA). All these approaches entail complicated mass-manufacturing issues, which have either not yet been solved or require elaborate control mechanisms and fine tolerances; both of which greatly increase costs to the point where it is difficult to produce a disposable product.
Another major concern with existing drug delivery devices is the difficulty of making such a complex mechanism (and its associated electronics) waterproof. This issue is tackled either by the users being very careful not to get it wet, or by a complex sealing of the mechanism package. Said sealing is inherently difficult with permanent pump devices where new disposable infusion sets need to be periodically attached to the device.
Accordingly, the achievement of a novel battery cell capable of a significant displacement (that is one capable of effectively driving a drug delivery device and herein referred to as a “displacement-generating battery”) allows for a unique, beneficial, simpler and therefore more inexpensive solution for drug-delivery devices to be attained. Notably, such a drug-delivery device, in its simplest embodiment, would not require any mechanical or hydraulic amplification and thus would represent an advance in the art, as it would enable direct displacement of a drug in a reservoir within said drug-delivery device by said battery cell. In some embodiments of this invention the battery cell displaces a disc, plate, diaphragm, or piston as a coupling component located between the battery cell and the drug reservoir that in turn displaces a liquid drug in the reservoir within said drug-delivery device. In addition, since the displacement generated by the battery is directly related to the accumulated electric discharge in the battery, the extent of the displacement of a drug in a reservoir can be very accurately controlled.
Accordingly, there is a need for an inexpensive drug-delivery device which is capable of very precise actions while only requiring low manufacturing tolerances, and is simple to operate with minimal requirements for internal control/feedback mechanisms.
It is still further object of embodiments of the present invention to provide a drug-delivery device whose delivery rate and volume of drug delivered is accurately controlled by an electrochemical reaction, and specifically, by an electrochemical reaction that causes a volume or shape change that actuates the delivery of the drug. In a preferred embodiment the volume change is positive, that is, the displacement is positive.
It is still further object of embodiments of the present invention to provide a displacement-generating battery that is used as an actuator which transmits a displacement resulting from an electrochemical reaction via a coupling component in such a manner that a drug contained within a drug reservoir affected by the coupling is forced through an administration means into the body of a patient.
It is also the object of embodiments of the present invention to provide a drug-delivery device which is relatively insensitive to temperature and pressure changes.
It is a further object of embodiments of the present invention to provide a drug-delivery device where the energy derived from the discharge of said battery provides the main power source for said delivery.
It is a still further object of embodiments of the present invention to provide a drug-delivery device with a minimum of moving parts.
It is a still further object of embodiments of the present invention to provide a drug-delivery device with inherent position determination. In one embodiment of the present invention the inherent position determination is achieved via a Hall sensor and a magnet, where the distance between them varies with the displacement thereby causing changes in the detected magnetic field that can be sensed by the drug-delivery device.
It is a still further object of embodiments of the present invention to provide a drug-delivery device which does not suffer from an unacceptable lag in response time.
It is a still further object of embodiments of the present invention to provide a drug-delivery device which is inherently waterproof.
It is a still further object of embodiments of the present invention to provide a drug-delivery device where control and maintenance issues are simpler than in existing approaches and with less potential failure modes.
It is a still further object of embodiments of the present invention to provide a drug-delivery device in which the displacement-generating battery also provides the power to operate the electronics of the device thus advantageously obviating the need for having a further battery cell to power the electronics of the drug-delivery device and so the device is simplified, made more efficient, and lowered in cost.
These and other objects of embodiments of the present invention will become more evident in the summary of the invention and in the description of the preferred embodiment.